RESUMO
The purpose of our study was to compare progression-free survival and quality of life (QOL) after cisplatin-gemcitabine (CG) or epirubicin-gemcitabine (EG) in chemotherapy-naive patients with unresectable non-small-cell lung cancer. Patients (n=240) were randomised to receive gemcitabine 1125 mg x m(-2) (days 1 and 8) plus either cisplatin 80 mg x m(-2) (day 2) or epirubicin 100 mg x m(-2) (day 1) every 3 weeks for a maximum of five cycles. Eligible patients had normal organ functions and Eastern Cooperative Oncology Group performance status Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
, Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
, Desoxicitidina/análogos & derivados
, Neoplasias Pulmonares/tratamento farmacológico
, Adenocarcinoma/tratamento farmacológico
, Adenocarcinoma/patologia
, Adenocarcinoma/secundário
, Adulto
, Idoso
, Idoso de 80 Anos ou mais
, Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
, Carcinoma de Células Grandes/tratamento farmacológico
, Carcinoma de Células Grandes/patologia
, Carcinoma de Células Grandes/secundário
, Carcinoma Pulmonar de Células não Pequenas/patologia
, Carcinoma de Células Escamosas/tratamento farmacológico
, Carcinoma de Células Escamosas/patologia
, Carcinoma de Células Escamosas/secundário
, Cisplatino/administração & dosagem
, Desoxicitidina/administração & dosagem
, Epirubicina/administração & dosagem
, Feminino
, Humanos
, Neoplasias Pulmonares/patologia
, Masculino
, Pessoa de Meia-Idade
, Estadiamento de Neoplasias
, Prognóstico
, Qualidade de Vida
, Taxa de Sobrevida
, Resultado do Tratamento
, Gencitabina
RESUMO
The aim of the study was to evaluate efficacy and tolerance of epirubicin and gemcitabine as first-line chemotherapy in patients with advanced non-small-cell lung cancer. A phase I study was performed with the combination of escalating doses of epirubicin intravenously on day 1 and a fixed dose of gemcitabine on days 1 and 8 of a 21 -day cycle. Eighteen patients were included in the phase I part of the study before the maximum tolerated dose was found. Dose-limiting toxicity was febrile neutropenia. The phase II part of the study was continued with epirubicin 100 mg m(-2) on day 1 and gemcitabine 1125 mg m(-2) on days 1 and 8 of a 21-day cycle. Forty-three chemotherapy-naive patients were included. The median age of the patients was 60 years (range 26-75). Most patients (74%) were in stage IV. Granulocytopenia CTC grade 4 occurred in 32.5% and thrombocytopenia grade 4 in 11.6% of cycles. Febrile neutropenia occurred in six patients. Non-haematological toxicity was mainly mucositis CTC grade 2 and 3 in 35% of patients. The tumour response rate was 49% (95% confidence interval (CI) 35-63%). The median survival time for the patients was 42 weeks (95% CI 13-69).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Epirubicina/administração & dosagem , Humanos , Qualidade de Vida , GencitabinaRESUMO
Acute exacerbations of Pseudomonas aeruginosa lung infections were treated with ceftazidime (CTZ) by continuous infusion (CI) in eight adult cystic fibrosis (CF) patients. CTZ pharmacokinetics were studied after a single dose and during CI (100 mg/kg/24 h) with a CADD-PLUS infusion pump at home for 3 weeks. Individual CTZ pharmacokinetic parameters after single-dose administration were a half-life (t1/2 beta) of 1.90 +/- 0.85 h (mean +/- SD), a volume of distribution (Vs) of 0.28 +/- 0.08 L/kg, and a total body clearance (CL) of 0.152 +/- 0.014 L/h/kg. CL during CI was 0.147 +/- 0.019 L/h/kg, equal to the CL after a single dose. CTZ clearance at the start and at the end of the treatment did not differ. The mean fraction of the dose recovered from the urine was 92.6% (range 85.6-98.5%). Renal clearance was 0.147 +/- 0.015 L/h/kg and was not influenced by the pulmonary exacerbation. The early-morning serum concentrations were significantly higher than the afternoon levels (p < 0.02). The mean CTZ serum concentration during CI was 28.7 +/- 5.0 mg/L. Clinical condition and quality of life improved significantly during and after treatment. With the pharmacokinetic population data from the single-dose study, the CTZ steady-state concentrations during CI could be predicted [precision (root mean squared prediction error) 3.1 mg/L; bias (mean prediction error) 0.4 mg/L]. This method may serve as a model in the development of CTZ continuous-infusion dosage regimens in CF home treatment.